The work proposed represents a continuation of our exploitation of heritably different inbred mouse strains to uncover and understand genetic factors involved in the regulation of the immune response. We have determined that spleens from different mouse strains differ in the number of plaque forming cells responding to certain well characterized antigens. Moreover, mouse strains differ in their in vivo vs in vitro (cell suspension) response in characteristic ways. The genetic bases of these responses have been partially characterized with a series of hybrid crosses and backcrosses. We propose to utilize this information to experimentally attack the following questions: 1) Do genes which control the number of antibody- producing cells in vivo act exclusively within immunocompetent cells or do they also act in other cells which then decisively determine the extracellular environment of immunocompetent cells? 2) Are such genes expressed equivalently or differentially within thymus derived vs bone marrow derived cells? 3) Are the genetically controlled effects on the in vivo response related to other described regulatory mechanisms: the suppresion of antibody synthesis by thyms cells or by cells possessing histamine receptors on their surface?